How minor structural changes generate major consequences in photophysical properties of RE coordination compounds; resonance effect, LMCT state

Lanthanide coordination compounds of the formula Na[Ln(L)4] (1Ln), where Ln ¼ La3þ, Eu3þ, Gd3þ, Tb3þ, L ¼ [L] and HL ¼ dimethyl(4-methylphenylsulfonyl)amidophosphate, were synthesized. Their structural and spectroscopic properties were discussed in detail based on X-ray diffraction measurements, IR spectroscopy, absorption and emission spectroscopy at 293 and 77 K and theoretical calculations of the intramolecular energy transfer (IET) rates. DFT calculations were used to investigate the 1Ln electronic properties required to calculate the transition rates. 30 and 22 pathways of intramolecular nonradiative energy transfer were examined in the case of 1Eu and 1Tb, respectively. It is shown that the main pathway for sensitization of the lanthanide emission is either the triplet (1Eu) or singlet (1Tb) transfer, occurring mainly through the exchange mechanism. The energy rates for energy transfer from S1 and T1 equal WS ¼ 1:53 105 s 1 (1Eu), WT ¼ 5:14 106 s 1 (1Eu) and WS ¼ 4:09 107 s 1 (1Tb), WT ¼ 6:88 105 s 1 (1Tb). The crucial role of the 7F5 level in the energy transfer process of 1Tb and the participation of the LMCTstate in the depopulation of the ligand singlet state of 1Eu were demonstrated. The influence of the resonance effect on the splitting of the 7F1 level in 1Eu was analyzed. By comparing the properties of 1Ln with the properties of 2Ln coordination compounds, sharing the same ligand and crystallizing in the same crystallographic system (monoclinic), but with a different space group, it is demonstrated how slight structural changes can affect the photophysical properties of Ln compounds.publishe

The Alternative Splice Variant of Protein Tyrosine Kinase 6 Negatively Regulates Growth and Enhances PTK6-Mediated Inhibition of β-Catenin

Protein tyrosine kinase 6 (PTK6), also called breast tumor kinase (BRK), is expressed in epithelial cells of various tissues including the prostate. Previously it was shown that PTK6 is localized to epithelial cell nuclei in normal prostate, but becomes cytoplasmic in human prostate tumors. PTK6 is also primarily cytoplasmic in the PC3 prostate adenocarcinoma cell line. Sequencing revealed expression of wild type full-length PTK6 transcripts in addition to an alternative transcript lacking exon 2 in PC3 cells. The alternative transcript encodes a 134 amino acid protein, referred to here as ALT-PTK6, which shares the first 77 amino acid residues including the SH3 domain with full length PTK6. RT-PCR was used to show that ALT-PTK6 is coexpressed with full length PTK6 in established human prostate and colon cell lines, as well as in primary cell lines derived from human prostate tissue and tumors. Although interaction between full-length PTK6 and ALT-PTK6 was not detected, ALT-PTK6 associates with the known PTK6 substrates Sam68 and β-catenin in GST pull-down assays. Coexpression of PTK6 and ALT-PTK6 led to suppression of PTK6 activity and reduced association of PTK6 with tyrosine phosphorylated proteins. While ALT-PTK6 alone did not influence β-catenin/TCF transcriptional activity in a luciferase reporter assay, it enhanced PTK6-mediated inhibition of β-catenin/TCF transcription by promoting PTK6 nuclear functions. Ectopic expression of ALT-PTK6 led to reduced expression of the β-catenin/TCF targets Cyclin D1 and c-Myc in PC3 cells. Expression of tetracycline-inducible ALT-PTK6 blocked the proliferation and colony formation of PC3 cells. Our findings suggest that ALT-PTK6 is able to negatively regulate growth and modulate PTK6 activity, protein-protein associations and/or subcellular localization. Fully understanding functions of ALT-PTK6 and its impact on PTK6 signaling will be critical for development of therapeutic strategies that target PTK6 in cancer

Thermodynamics of Mixtures Containing Amines. XV. Liquid–Liquid Equilibria for Benzylamine + CH3(CH2)nCH3 (n = 8, 9, 10, 12, 14)

Coexistence curves for the liquid−liquid equilibria (LLE) of 1-phenylmethanamine (benzylamine) + CH3(CH2)nCH3 (n = 8, 9, 10, 12, 14) have been determined using the critical opalescence method by means of a laser scattering technique. All of the LLE curves show an upper critical solution temperature (UCST), which increases with increasing n. For systems including a given n-alkane, the UCST decreases in the sequence aniline > 2-methylaniline (o-toluidine) > benzylamine > N-methylaniline > pyridine. This means that amine−amine interactions become weaker in the same order. Most of the DISQUAC interaction parameters for the aliphatic/amine (a,n) and aromatic/ amine (b,n) contacts previously determined for solutions with aniline, o-toluidine, or N-methylaniline have been used for the representation of the LLE data. Only the first dispersive interaction parameter of the (a,n) contact has been modified. The coordinates of the critical points are correctly represented by the model

The Four types of Tregs in malignant lymphomas

Regulatory T cells (Tregs) are a specialized subpopulation of CD4+ T cells, which act to suppress the activation of other immune cells. Tregs represent important modulators for the interaction between lymphomas and host microenvironment. Lymphomas are a group of serious and frequently fatal malignant diseases of lymphocytes. Recent studies revealed that some lymphoma T cells might adopt a Treg profile. Assessment of Treg phenotypes and genotypes in patients may offer prediction of outcome in many types of lymphomas including diffuse large B-cell lymphoma, follicular lymphoma, cutaneous T cell lymphoma, and Hodgkin's lymphoma. Based on characterized roles of Tregs in lymphomas, we can categorize the various roles into four groups: (a) suppressor Tregs; (b) malignant Tregs; (c) direct tumor-killing Tregs; and (d) incompetent Tregs. The classification into four groups is significant in predicting prognosis and designing Tregs-based immunotherapies for treating lymphomas. In patients with lymphomas where Tregs serve either as suppressor Tregs or malignant Tregs, anti-tumor cytotoxicity is suppressed thus decreased numbers of Tregs are associated with a good prognosis. In contrast, in patients with lymphomas where Tregs serve as tumor-killing Tregs and incompetent Tregs, anti-tumor cytotoxicity is enhanced or anti-autoimmune Tregs activities are weakened thus increased numbers of Tregs are associated with a good prognosis and reduced numbers of Tregs are associated with a poor prognosis. However, the mechanisms underlying the various roles of Tregs in patients with lymphomas remain unknown. Therefore, further research is needed in this regard as well as the utility of Tregs as prognostic factors and therapy strategies in different lymphomas

Staphylococcal enterotoxin A (SEA) stimulates STAT3 activation and IL-17 expression in cutaneous T-cell lymphoma

Cutaneous T-cell lymphoma (CTCL) is characterized by proliferation of malignant T cells in a chronic inflammatory environment. With disease progression, bacteria colonize the compromised skin barrier and half of CTCL patients die of infection rather than from direct organ involvement by the malignancy. Clinical data indicate that bacteria play a direct role in disease progression, but little is known about the mechanisms involved. Here, we demonstrate that bacterial isolates containing staphylococcal enterotoxin A (SEA) from the affected skin of CTCL patients, as well as recombinant SEA, stimulate activation of signal transducer and activator of transcription 3 (STAT3) and upregulation of interleukin (IL)-17 in immortalized and primary patient-derived malignant and nonmalignant T cells. Importantly, SEA induces STAT3 activation and IL-17 expression in malignant T cells when cocultured with nonmalignant T cells, indicating an indirect mode of action. In accordance, malignant T cells expressing an SEA-nonresponsive T-cell receptor variable region β chain are nonresponsive to SEA in monoculture but display strong STAT3 activation and IL-17 expression in cocultures with SEA-responsive nonmalignant T cells. The response is induced via IL-2 receptor common γ chain cytokines and a Janus kinase 3 (JAK3)-dependent pathway in malignant T cells, and blocked by tofacitinib, a clinical-grade JAK3 inhibitor. In conclusion, we demonstrate that SEA induces cell cross talk-dependent activation of STAT3 and expression of IL-17 in malignant T cells, suggesting a mechanism whereby SEA-producing bacteria promote activation of an established oncogenic pathway previously implicated in carcinogenesis

Malignant inflammation in cutaneous T-cell lymphoma: a hostile takeover

Cutaneous T-cell lymphomas (CTCL) are characterized by the presence of chronically inflamed skin lesions containing malignant T cells. Early disease presents as limited skin patches or plaques and exhibits an indolent behavior. For many patients, the disease never progresses beyond this stage, but in approximately one third of patients, the disease becomes progressive, and the skin lesions start to expand and evolve. Eventually, overt tumors develop and the malignant T cells may disseminate to the blood, lymph nodes, bone marrow, and visceral organs, often with a fatal outcome. The transition from early indolent to progressive and advanced disease is accompanied by a significant shift in the nature of the tumor-associated inflammation. This shift does not appear to be an epiphenomenon but rather a critical step in disease progression. Emerging evidence supports that the malignant T cells take control of the inflammatory environment, suppressing cellular immunity and anti-tumor responses while promoting a chronic inflammatory milieu that fuels their own expansion. Here, we review the inflammatory changes associated with disease progression in CTCL and point to their wider relevance in other cancer contexts. We further define the term "malignant inflammation" as a pro-tumorigenic inflammatory environment orchestrated by the tumor cells and discuss some of the mechanisms driving the development of malignant inflammation in CTCL

Causes of interference methane fermentation

Biogazownie rolnicze stają się w Polsce coraz powszechniejsza i obiecującą droga pozyskiwania energii odnawialnej. Jakość powstającego biogazu podczas procesu fermentacji metanowej uzależniona jest od zawartości metanu - głównego składnika biogazu. Przeciętna ilość tego gazu kształtuje sięw granicach 45-65%. Oczywistym jest, iż w głównej mierze uzależnione jest to od samego substratu, który wprowadzamy do bioreaktora. Jednakże niezmiernie ważnym aspektem jest zwrócenie uwagi na zawartość inhibitorów fermentacji, czyli wszelkich substancji bądź związków, które mogą zakłócić proces. W artykule omówione zostało zagadnienie dotyczące zahamowania lub załamania procesu fermentacji metanowej spowodowane występowaniem tzw. inhibitorów fermentacji.The article discusses the issue of problems with the inhibition of methane fermentation process or the collapse to the occurrence causing of the so-called fermentation inhibitors. Agricultural biogas plants in Poland are becoming increasingly common and promising way for renewables. The quality of the resulting biogas methane fermentation process depends on the content of methane - the main component of biogas. The average amount of this gas ranges from 45-65%. It is obvious that mainly depends amount of methane on the substrate, which introduced to the bioreactor. However, parameters of the process and content of fermentation inhibitors or other compounds are regarded as crucial factors for keeping the fermentation process on proper level